Human malignant melanoma usually starts as harmless moles that undergo radial to invasive growth and end in the destructive stage of metastatic melanoma. Melanoma usually resists chemotherapy and radiotherapy. Surgery is the most effective treatment. Early diagnosis is required for surgery to be effective, which is unfortunately hampered by the lack of markers that are sensitive and specific for melanoma.
The commonly used antibodies for immuno-histochemical diagnosis of melanoma are HMB-45, anti-S-100 and NKI/C3 (for a review, please see Smoller B R, “Immunohistochemistry in the Diagnosis of Melanocytic Neoplasms”, in PATHOLOGY: State of the Art Reviews, 2:371–383, 1994).
HMB-45 has been shown to react with the melanoma-associated antigen gp-100. Adema G J, de-Boer A J, Vogel A M, Loenen W A, Figdor C G: Molecular characterization of the melanocyte lineage-specific antigen gp 100. J. Biol. Chem. 1994; 269:20126–20133. HMB-45 reacts with melanoma, junctional nevi, dysplastic nevi, spindle cell and epitheloid cell nevi, congenital nevi and blue nevi. Gown A M, Vogel A M, Hoak D, Gough F, McNutt M A: Monoclonal antibodies specific for melanocytic tumors distinguish subpopulations of melanocytes. Am. J. Pathol. 1986; 123:195–203; Esclamado R M, Gown A M, Vogel A M. Unique proteins defined by monoclonal antibodies specific for human melanoma. Some potential clinical applications. Am. J. Surg. 1986; 152:376–385; Palazzo J, Duray P H: Typical, dysplastic, congenital, and Spitz nevi: a comparative immuno-histochemical study. Hum Pathol 1989; 20:341–346; Smoller B R, McNutt N S, Hsu A: HMB-45 recognizes stimulated melanocytes. J. Cutan. Pathol. 1989; 16:49–53; Smoller B R, McNutt N S, Hsu A: HMB-45 staining of dysplastic nevi. Support for a spectrum of progression toward melanoma. Am J Surg Pathol 1989; 13:680–684; Sun J, Morton T H Jr., Gown A M: Antibody HMB-45 identifies the cells of blue nevi. An immuno-histochemical study on paraffin sections. Am J Surg Pathol 1990; 14:748–751. HMB-45 is routinely used as a marker to differentiate melanoma from nonmelanocytic cancer cells. Herrera G A, Hancock C. Specificity of antibody HMB-45. Arch. Pathol. La. Med. 1992; 116:900–901. However, diagnosis with HMB-45 leaves a sizable numbers of melanomas undetected because the sensitivity of HMB-45 is between 67% and 93%. Wick M R, Swanson P E, Rocamora A. Recognition of malignant melanoma by monoclonal antibody HMB-45. An immuno-histochemical study of 200 paraffin-embedded cutaneous tumors. J Cutan Pathol 1988; 15:201–207; Ordonez N G, Ji X L, Hickey R C: Comparison of HMB-45 monoclonal antibody and S100 protein in the immuno-histochemical diagnosis of melanoma. Am. J. Clin. Pathol. 1988; 90:385–390.
Antibodies to S-100 protein have higher sensitivity than HMB-45 with malignant melanoma varieties. Nakajima T, Watanabe S, Sato Y, Kameya T, Shimosato Y, Ishihara K: Immuno-histochemical demonstration of S100 protein in malignant melanoma and pigmented nevus and its diagnostic application. Cancer 1982; 50:912–918; Kindblom L G, Lodding P, Rosengren L, Baudier J, Haglid K: S100 protein in melanocytic tumors. An immuno-histochemical investigation of benign and malignant melanocytic tumors and metastases of malignant melanoma and a characterization of the antigen in comparison to human brain. Acta. Pathol. Microbiol Immunol. Scand. 1984; 92:219–230; Springall D R, Gu J, Cocchia D, Michetti F, Levene A, Levene M M et al: The value of S100 immunostaining as a diagnostic tool in human malignant melanomas. A comparative study using S100 and neuron-specific enolase antibodies. Virchows Arch. Pathol. Anat. Histopathol. 1983; 400:331–343; Cochran A J, Wen D R, Herschman H R, Gaynor R B: Detection of S100 protein as an aid to the identification of melanocytic tumors. Int. J. Cancer 1982; 30:295–297; Gatter K C, Ralfkiaer E, Skinner J, Brown D, Heryet A, Pulford K A et al: An immunocytochemical study of malignant melanoma and its differential diagnosis from other malignant tumors. J Clin Pathol 1985; 38:1353–1357; Hachisuka H, Sakamoto F, Nomura H, Mori O, Sasai Y: Immuno-histochemical study of S100 protein and neuron specific enolase (NSE) in melanocytes and the related tumors. Acta Histochem. 1986; 80:215–223; Argenyi Z B, Cain C, Bromley C, Nguyen A V, Abraham A A, Kerschmann R et al: S100 protein-negative malignant melanoma: fact or fiction? A light-microscopic and immuno-histochemical study. Am. J. Dermatopathol. 1994; 16:233–240 (11–17). However, anti-S100 antibodies are notoriously unspecific. Anti-S100 antibodies have been shown to stain benign cells such as salivary and sweat glands, skeletal and cardiac muscle, histiocytes, Schwann cells, lipocytes, chondrocytes, astrocytes, oligodendrocytes (Kindblom L G, Lodding P, Rosengren L, Baudier J, Haglid K: S100 protein in melanocytic tumors. An immuno-histochemical investigation of benign and malignant melanocytic tumors and metastases of malignant melanoma and a characterization of the antigen in comparison to human brain. Acta. Pathol. Microbiol Immunol. Scand. 1984; 92:219–230; Stefansson K, Wollmann R L, Moore B W, Arnason B G. S100 protein in human chondrocytes. Nature 1982; 295:63–64; Stefansson K, Wollmann R L, Moore B W: Distribution of S100 protein outside the central nervous system. Brain Res. 1982; 234:309–317) and tumors arising from these cells (Tabuchi K, Moriya Y, Furuta T, Ohnishi R, Nishimoto: A S100 protein in human glial tumors. Qualitative and quantitative studies. Acta Neurochir Wien 1982; 65:239–251; Vanstapel M J, Gatter K C, de Wolf Peeters C, Mason D Y, Desmet V D. New sites of human S100 immunoreactivity detected with monoclonal antibodies. Am J Clin Pathol 1986; 85:160–168). Anti-S100 antibodies have also been shown to stain many non-melanoma malignant tumor tissues. Drier J K, Swanson P E, Cherwitz D L, Wick M R: S100 protein immunoreactivity in poorly differentiated carcinomas. Immuno-histochemical comparison with malignant melanoma. Arch. Pathol. Lab. Med. 1987; 111:447–452.
NKI/C3 antibody also reacts with a broad range of benign and malignant neoplasms. Mackie R M, Campbell I, Turbitt M L. Use of NK1 C3 monoclonal antibody in the assessment of benign and malignant melanocytic lesions. J Clin Pathol 1984; 37:367–372; Vennegoor C, Calafat J, Hageman P, van Buitenen F, Janssen H, Kolk A et al. Biochemical characterization and cellular localization of a formalin-resistant melanoma-associated antigen reacting with monoclonal antibody NKI/C-3. Int. J. Cancer 1985; 35:287–295. These unspecific activities limit the usefulness of NKI/C3 antibody in the diagnosis of melanocytic lesions.
KBA.62 antibody is comparable to HMB-45 in its sensitivity to melanoma, but is less specific than HMB-45 in that KBA.62 stains squamous cell carcinoma and basal cell carcinomas. Cohen Knafo E, al Saati T, Aziza J, Ralfkiaer E, Selves J, Gorguet B et al: Production and characterisation of an antimelanoma monoclonal antibody KBA.62 using a new melanoma cell line reactive on paraffin wax embedded sections. J Clin Pathol 1995; 48:826–831.